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Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak

Sankaranarayanan, R; Li, Y; Greensmith, DJ; Eisner, DA; Venetucci, L

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Authors

R Sankaranarayanan

Y Li

DA Eisner

L Venetucci



Abstract

In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterised the effects of two forms of Ca leak (Ca-sensitising and non-sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca2+]i with fluo-3 in voltage-clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non-sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca2+]i, increased diastolic [Ca2+]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l−1) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the biphasic decay was replaced by slow decay. We conclude that, in the presence of adrenergic stimulation, Ca leak can produce biphasic decay; the slow phase results from the leak opposing Ca uptake by SERCA. The degree of leak determines whether decay of Ca waves, biphasic or monophasic, occurs.

Citation

Sankaranarayanan, R., Li, Y., Greensmith, D., Eisner, D., & Venetucci, L. (2016). Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak. Journal of Physiology, 594(3), 611-623. https://doi.org/10.1113/JP271473

Journal Article Type Article
Acceptance Date Oct 30, 2015
Online Publication Date Nov 5, 2015
Publication Date Jan 1, 2016
Deposit Date Feb 3, 2016
Publicly Available Date Apr 5, 2016
Journal The Journal of Physiology
Print ISSN 0022-3751
Electronic ISSN 1469-7793
Publisher Wiley
Volume 594
Issue 3
Pages 611-623
DOI https://doi.org/10.1113/JP271473
Publisher URL http://dx.doi.org/10.1113/JP271473
Related Public URLs http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1469-7793/

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